Use of a new stimulation design to treat neurological disorder

ABSTRACT

The method and system described herein relate to stimulating nerve tissue using a pulse generator. A stimulus is created that comprises a signal that is produced from a frequency spectrum having a power spectral density per unit of bandwidth proportional to 1/f β , wherein β is excludes 0. The stimulus is provided from the pulse generator to at least one stimulation lead; and applied to nerve tissue via one or several electrodes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.61/378,249, filed Aug. 30, 2010, which is incorporated herein byreference.

TECHNICAL FIELD

The present invention relates to a method which can be utilized to treatneurological conditions and/or disorders. More particularly, and not byway of limitation, the present invention is directed to a method forusing 1/f^(β) noise to treat neurological conditions and/or disorders.

BACKGROUND OF THE INVENTION

Different firing modes or frequencies occur in the brain and/or otherneuronal tissue, for example tonic firing and burst firing (irregular orregular burst firing). Such firing modes can be utilized for normalprocessing of information, however, alteration of the firing modes, mayalso lead to pathology.

For example, certain neurological conditions are associated withhyperactivity of the brain and can be traced to a rhythmic burst firingor high frequency tonic firing or hypersynchronous firing (e.g.,tinnitus, pain, and epilepsy). Other conditions can be associated withan arrhythmic burst firing or a dysynchronous firing, for example,movement disorders, hallucinations, persistent vegetative state (PVS),multiple chemical sensitivity (MCS), or hypofunctioning for example,hypoesthesia, depression, hearing loss, visual loss, dysthymia, chronicfatigue etc.

During the past decade, neuromodulation systems have been used tomodulate various areas of the brain, spinal cord, or peripheral nerves(See, for example, U.S. Pat. Nos. 6,671,555; 6,690,974). These types ofsystems utilize tonic forms of electrical stimulation. Recently bursttranscranial magnetic stimulation (TMS) at theta frequencies has beendeveloped (Huang et al., 2005). Theta burst TMS has been shown toproduce an effect on motor and visual cortex by suppressing excitatorycircuits after a short application period of only 20-190 s (Huang etal., 2005; Di Lazzaro et al., 2005; Franca et al., 2006).

Typically, the signals generated by the neuromodulation devices are notphysiological similar to the endogenous electrical signals generated bythe brain and the exogenous electrical signals generated by theneuromodulation devices typically result in epileptic events as well asthe brain habituates to these electrical signals in time. The inventoris the first to describe a neuromodulation design using parameters inwhich a 1/f^(β) noise is used to achieve stimulation of the tissue closeto physiological levels to treat a neurological condition.

BRIEF SUMMARY OF THE INVENTION

The method and system described herein relate to stimulating nervetissue to treat a neurological disease and/or condition. Using a pulsegenerator, a stimulus is created that comprises a signal that isproduced from a frequency spectrum having a power spectral density perunit of bandwidth proportional to 1/f^(β), wherein β excludes 0. β canbe, for example, any real, natural, integer, rational, irrational,complex or fluctuating number. For example, β=1 or β=2. The stimulus isprovided from the pulse generator to at least one stimulation lead; andapplied to nerve tissue of the patient via one or several electrodes ofthe at least one stimulation lead.

Yet further, the stimulus can be combined with at least one pulsestimulus repeated in a tonic manner or a burst stimulus that comprises aplurality of groups of spike pulses.

Still further, the stimulus can be modulated at any specific frequency,either by selective power increase, envelope modulation or adding moretonic or burst stimuli of this frequency.

A first stimulation parameter that defines a frequency having a lowerbound of a frequency spectrum and a second stimulation that defines afrequency having an upper bound of a frequency spectrum can be stored ina controller or pulse generator and such controller can be used togenerate a stimulus that comprises a frequency spectrum between thefirst and second stimulation parameters such that the frequency andpower of the frequency spectrum are inversely proportional.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

In the following section, the invention will be described with referenceto exemplary embodiments illustrated in the figures, in which:

FIGS. 1A-1J illustrate example electrical stimulation leads that may beused to electrically stimulate neuronal tissue.

FIG. 2 depicts an implantable pulse generator that may be programmed togenerate stimulation according to one representative embodiment.

FIGS. 3A and 3B illustrate pink noise or 1/f noise. FIG. 3A shows anexemplary pink noise spectrum. FIG. 3B shows an exemplary pink noisespectrum generated by a power source, for example an external orimplantable generator

FIGS. 4A and 4B illustrate red, brown or Brownian noise or 1/f² noise.FIG. 4A shows an exemplary red or Brown(ian) noise spectrum. FIG. 4Bshows an exemplary spectrum generated by a power source, for example anexternal or implantable generator.

FIGS. 5A-5B illustrate exemplary combinations of 1/f^(β) noise. FIG. 5Ashows 1/f^(β) noise modulated at alpha frequencies and FIG. 5B at1/f^(β) noise modulated at beta frequencies.

FIG. 6 depicts a stimulation system that can measure or detect givenneuronal signals that can be used to modulate the 1/f^(β) noisestimulation according to one representative embodiment.

FIG. 7 illustrates a 1/f^(β) spectrum at rest for normal and tinnituspatients. β is 2.2 for healthy controls, 1.5 for noise-like tinnitus and1.8 for pure tone tinnitus.

FIG. 8 depicts a stimulation system that can sense and/or monitor sleepstage that can be used to alter therapy.

FIG. 9 shows modules within the memory of FIG. 8.

DETAILED DESCRIPTION OF THE INVENTION

The following section more generally describes an example of a procedurefor treatment using a 1/f^(β) noise such as pink noise, red or brownnoise or black noise to optimize the following parameters; a set and/orrange of stimulation protocols that can most completely eliminateneurological disease/disorder, a set and/or range of stimulationprotocols that requires the lowest voltage, and a protocol thatmaintains treatment efficacy over long periods of time, for example, theprotocol can prevent habituation or adaptation and a protocol that isanti-epileptic. Still further, the generated 1/f^(β) noise signal can befiltered, combined, or otherwise processed, for example, whereby thegenerated 1/f^(β) noise is utilized as a background signal noise overanother signal with a spectral peak at a selected frequency. Forexample, an alpha peak, beta peak, delta peak and/or theta peak can beadded to the 1/f^(β) noise. The peaks can be generated using typicalknown frequencies or the peaks can be individualized for each patient.Yet further, the 1/f^(β) noise can be combined with standard tonicand/or burst stimulation to further enhance the optimization or preventhabituation. Combinations of tonic and/or burst stimulation are known inthe art, for example, U.S. Pat. No. 7,734,340, issued Jun. 8, 2010 andU.S. application Ser. No. 12/109,098, filed Apr. 24, 2008, which areincorporated by reference in their entirety.

The predetermined site for stimulation can include, for example,peripheral neuronal tissue and/or central neuronal tissue. Peripheralneuronal tissue can include a nerve root or root ganglion or anyperipheral neuronal tissue associated with a given dermatome or anyneuronal tissue that lies outside the brain, brainstem or spinal cord.

I. 1/f^(β) Noise

A noise signal can be described as a signal that is generated accordingto a random process. In practice, various algorithms (e.g., in softwareexecuted on a processor) are employed to simulate a given random processto generate a “pseudo-random” signal where the generated pseudo-randomsignal possesses similar characteristics with signals corresponding to acorresponding random process. The characteristics of a particular noisesignal depend upon the underlying process generating the noise signal.For example, the power spectral density or power distribution in thefrequency domain may be employed to characterize the random process and,hence, also characterize a corresponding time-domain noise signal. Theclassification of the power spectral density of a noise signal may bedescribed in reference to color or color terminology with differenttypes of power spectral densities named after different colors.

According to these conventions, the power spectral density is defined asbeing inversely proportional to 1/f^(β), where f represents frequencyand β is a value selected to characterize the noise signal. The value βcan be for example, any real, natural, integer, rational, irrational orcomplex number. For example, the spectral density for white noise isflat (β=0), for pink noise or flicker noise β=1 and for Brownian or rednoise β=2 and black noise is β>2. Suitable non-integer β values about 1include 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.5, or any valuesthere between for some embodiments. Likewise, suitable non-integer βvalues about 2 can include 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4,2.5 or any value there between for some embodiments.

Abnormal electrical and/or neural activity is associated with differentdiseases and disorders in the central and peripheral nervous systems. Inaddition to a drug regimen or surgical intervention, potentialtreatments for such diseases and disorders include the implantation of amedical device (for example, an implantable pulse generator (IPG)) in apatient for electrical stimulation of the patient's body tissue. Inparticular, an implantable medical device may electrically stimulate atarget neuronal tissue location by the selective application ofcontrolled electrical input signals to one or more electrodes coupled toor placed in proximity to the patient's neuronal tissue. Such electricalinput signals may be applied to the patient's neuronal tissue in orderto treat a neurological disease, condition, or disorder.

The response of nonlinear systems to a weak input signal may beoptimized by combining the input signal with a non-negligible level ofnoise or as known in the art as stochastic resonance. For a system toexhibit stochastic resonance there needs to be a threshold that must beexceeded in order to activate the system. When the input signal is notstrong enough to exceed the threshold, small amounts of noise addedeither to the system or the signal may occasionally suffice to triggeractivation. Typically this type of phenomenon is associated with whitenoise.

Over time, a repetitive electrical stimulation signal, such as typicalelectrical stimulation performed today, that is dissimilar to thebrain's own naturally-occurring signals may become less effective as thebrain “filters out” or “ignores” the signal. Hence, a problem withstandard electrical stimulation parameters used today is habituationbecause the electrical stimulation parameters result in a repetitiveelectrical signal and thus, the brain habituates to the signal oradapts. It is believed that naturally-occurring signals within the humanbrain closely resemble 1/f^(β) noise. Because of this, the efficacy ofelectrical stimulation signals applied to neuronal tissue is improved bymaking those signals comport as closely as possible to the brain's ownsignals. Such a signal may be less likely to lose effectiveness overtime. One way to comport an electrical stimulation signal to resemblethe brain's own signals is to utilize a stimulation paradigm thatresembles that of the brain's normal signals, for example convert thepink noise spectrum into electrical stimulation signals that can beapplied to the desired neuronal tissue at a desired pattern, frequency,amplitude such that it maintains parameters associated with 1/f^(β)noise spectrum. To further modulate the 1/f^(β) noise stimulationparadigm, add specific peak frequencies to the 1/f^(β) noise stimulationparadigm that are known or associated with given brain areas, forexample, add an alpha frequency peak to stimulate primary and secondarycortical areas; add a beta frequency peak to stimulate associationcortical areas, such as frontal cortex; add a theta frequency peak tostimulate the cingulate, hippocampus, amygdala; add a delta frequencypeak to stimulate the brainstem, ventral tegmental area (VTA), nucleusaccumbens/ventral medial prefrontal cortex (VMPFC). Yet further, blacknoise can be used to stimulate the brainstem and/or the reward system.These additional peak frequencies that are added to the 1/f^(β) noisestimulation paradigm can be obtained from the individual by EEG or MEGmeasurements or any other measurement to obtain the individual peakfrequency or the frequencies can be obtained from a database, forexample a database containing a list of given frequencies and spectralstructures for a brain structure or brain area. The frequency for eachbrain area, for example, each Brodmann area can be easily calculated bydefining a Brodmann area in source space and performing a spectralanalysis for that area using any software (i.e., sLORETA) to performsource analysis.

Still further, the 1/f^(β) noise stimulation paradigm can be modified byusing multiple poles or electrodes, for example, the stimulationparadigm is either sequentially cycled or randomly cycles through thepoles or electrodes upon the stimulation lead.

The 1/f^(β) noise can also be selected to specifically activate orinactivate a brain area or brain network, i.e., it can be chosen so asto not be normalizing, but to be non-physiological as to compensate foroveractivity or hypoactivity, followed at a later stage with normalphysiological 1/f^(β) noise stimulation parameters. For example duringsleep, changing the 1/f^(β) noise during sleep can improve memorystorage or prevent storage of memories, i.e., to prevent or treatposttraumatic stress disorder (PTSD).

II. Patient Selection

Subjects to be treated according to some representative embodiments canbe selected, identified and/or diagnosed based upon the accumulation ofphysical, chemical, and historical behavioral data on each patient. Oneof skill in the art is able to perform the appropriate examinations toaccumulate such data. One type of examination can include neurologicalexaminations, which can include mental status evaluations, which canfurther include a psychiatric assessment. Other types of assessments formovement disorders may include such assessments for example using theUnified Parkinson's Disease Rating Scale (UPDRS). Still further, othertypes of examinations can include, but are not limited to, motorexamination, cranial nerve examination, cognitive assessment andneuropsychological tests (i.e., Minnesota Multiphasic PersonalityInventory, Beck Depression Inventory, or Hamilton Rating Scale forDepression). Other types of assessment for tinnitus, for example, caninclude but are not limited to Visual Analogue Scales (VAS) and TinnitusHandicap Inventory (THI). In addition to neurological testing, routinehematological and/or biochemistry testing may also be performed.

In addition to the above examinations, imaging techniques can be used todetermine normal and abnormal brain function that can result indisorders. Thus, once the patient is identified from the above clinicalexaminations, imaging techniques can be further utilized to provide theregion of interest in which the electrodes are to be implanted.Functional brain imaging allows for localization of specific normal andabnormal functioning of the nervous system. This includes electricalmethods such as electroencephalography (EEG), magnetoencephalography(MEG), single photon emission computed tomography (SPECT), as well asmetabolic and blood flow studies such as functional magnetic resonanceimaging (fMRI), and positron emission tomography (PET) which can beutilized to localize brain function and dysfunction.

III. Implantation of Stimulation Leads

One or more stimulation leads 100, as shown in FIGS. 1A-1J are implantedsuch that one or more stimulation electrodes 102 of each stimulationlead 200 are positioned or disposed near, adjacent to, directly on oronto, proximate to, directly in or into or within the target tissue orpredetermined site. The leads shown in FIG. 1 are exemplary of manycommercially available leads, such as deep brain leads, percutaneousleads, paddle leads, etc. Examples of commercially available stimulationleads includes a percutaneous OCTRODE® lead or laminotomy or paddleleads or paddle structures such as PENTA® lead or LAMITRODE 44® lead allmanufactured by Advanced Neuromodulation Systems, Inc. For the purposesdescribed herein and as those skilled in the art will recognize, when anembedded stimulation system, such as the Bion®, is used, it ispositioned similar to positioning the lead 100.

Techniques for implanting stimulation electrodes are well known by thoseof skill in the art and may be positioned in various body tissues and incontact with various tissue layers; for example, deep brain, cortical,subdural, subarachnoid, epidural, cutaneous, transcutaneous andsubcutaneous implantation is employed in some embodiments.

A. Brain

Central neuronal tissue includes brain tissue, spinal tissue orbrainstem tissue. Brain tissue can include the frontal lobe, theoccipital lobe, the parietal lobe, the temporal lobe, the cerebellum, orthe brain stem. More specifically, brain tissue can include subcorticaltargets, for example, thalamus/sub-thalamus (i.e., thalamic nuclei,medial and lateral geniculate body, intralaminar nuclei, nucleusreticularis, pulvinar, subthalamic nuclei (STN), etc) basal ganglia(i.e., putamen, caudate nucleus, globus pallidus), hippocampus,amygdala, hypothalamus, epithalamus, mammilary bodies, ventral tegmentalarea (VTA), substantia nigra, corpus callosum, fornix, internal capsula,anterior and posterior commissural, cerebral peduncles etc. Brain tissuealso includes cerebellum, cerebellar peduncles, and cerebeller nucleisuch as fastigial nucleus, globose nucleus, dentate nucleus, emboliformnucleus. Still further, in addition to the above mentioned subcorticaltargets, brain tissue also includes cortical targets, for example,auditory cortex, prefrontal cortex, the dorsolateral prefrontal cortex,the ventromedial prefrontal cortex, the cingulate cortex, subcallosalarea, anterior cingulate cortex, the subgenual anterior cingulatecortex, the motor cortex and the somatosensory cortex. The somatosensorycortex comprises the primary, the secondary somatosensory cortex, andthe somatosensory association complex. Still further, the somatosensorycortex also includes Brodmann areas 1, 2, 3, 5, and 7. Yet further,brain tissue can include various Brodmann areas for example, but notlimited to Brodmann area 9, Brodmann area 10, Brodmann area 24, Brodmannarea 25, Brodmann area 32, Brodmann area 39, Brodmann area 41, Brodmannarea 42, and Brodmann area 46.

While not being bound by the description of a particular procedure,patients who are to have an electrical stimulation lead or electrodeimplanted into the brain for deep brain stimulation, generally, firsthave a stereotactic head frame, such as the Leksell, CRW, or Compass,mounted to the patient's skull by fixed screws. Subsequent to themounting of the frame, the patient typically undergoes a series ofmagnetic resonance imaging sessions, during which a series of twodimensional slice images of the patient's brain are built up into aquasi-three dimensional map in virtual space. This map is thencorrelated to the three dimensional stereotactic frame of reference inthe real surgical field. In order to align these two coordinate frames,both the instruments and the patient must be situated in correspondenceto the virtual map. The current way to do this is to rigidly mount thehead frame to the surgical table. Subsequently, a series of referencepoints are established to relative aspects of the frame and patient'sskull, so that either a person or a computer software system can adjustand calculate the correlation between the real world of the patient'shead and the virtual space model of the patient MRI scans. The surgeonis able to target any region within the stereotactic space of the brainwith precision (e.g., within 1 mm). Initial anatomical targetlocalization is achieved either directly using the MRI images orfunctional imaging (PET or SPECT scan, fMRI, MSI), or indirectly usinginteractive anatomical atlas programs that map the atlas image onto thestereotactic image of the brain. As is described in greater detailelsewhere in this application, the anatomical targets or predeterminedsite may be stimulated directly or affected through stimulation inanother region of the brain.

In addition to deep brain stimulation, cortical stimulation can also beused to stimulate various brain tissues. Any of the stimulation leadsillustrated in FIGS. 1A-1J can be used for cortical stimulation, as wellas any other cortical electrode or electrode array. For implantingconventional cortical electrodes, it typically requires a craniotomyunder general anesthesia to remove a relatively large (e.g.,thumbnail-sized or larger) window in the skull. A pilot hole (e.g., 4 mmor smaller) can be formed through at least part of the thickness of thepatient's skull adjacent a selected or predetermined site. In certainembodiments, the pilot hole can be used as a monitoring site.

The location of the pilot hole (and, ultimately the electrode receivedtherein) can be selected in a variety of fashions, for example, thephysician may use anatomical landmarks, e.g., cranial landmarks such asthe bregma or the sagittal suture, to guide placement and orientation ofthe pilot hole or the physician may use a surgical navigation system.Navigation systems may employ real-time imaging and/or proximitydetection to guide a physician in placing the pilot hole and in placingthe electrode in the pilot hole. In some systems, fiducials arepositioned on the patient's scalp or skull prior to imaging and thosefiducials are used as reference points in subsequent implantation. Inother systems, real-time MRI or the like may be employed instead of orin conjunction with such fiducials. A number of suitable navigationsystems are commercially available, such as the STEALTHSTATION TREON TGSsold by Medtronic Surgical Navigation Technologies of Louisville, Colo.,U.S.

Once the pilot hole is formed, the threaded stimulation lead may beadvanced along the pilot hole until the contact surface electricallycontacts a desired portion of the patient's brain. If the stimulationlead is intended to be positioned epidurally, this may compriserelatively atraumatically contacting the dura mater; if the electrode isto contact a site on the cerebral cortex, the electrode will be advancedto extend through the dura mater. Thus, the lead may be placedepidurally or subdurally for cortical stimulation.

B. Spinal Cord and/or Peripheral Nerves

Peripheral nerves can include, but are not limited to olfactory nerve,optic nerve, oculomotor nerve, trochlear nerve, trigeminal nerve,abducens nerve, facial nerve, vestibulocochlear (auditory) nerve,glossopharyngeal nerve, vagal nerve, accessory nerve, hypoglossal nerve,occipital nerve (e.g., suboccipital nerve, the greater occipital nerve,the lesser occipital nerve), the greater auricular nerve, the lesserauricular nerve, the phrenic nerve, brachial plexus, radial axillarynerves, musculocutaneous nerves, radial nerves, ulnar nerves, mediannerves, intercostal nerves, lumbosacral plexus, sciatic nerves, commonperoneal nerve, tibial nerves, sural nerves, femoral nerves, glutealnerves, thoracic spinal nerves, obturator nerves, digital nerves,pudendal nerves, plantar nerves, saphenous nerves, ilioinguinal nerves,gentofemoral nerves, and iliohypogastric nerves. Furthermore, peripheralneuronal tissue can include but is not limited to peripheral nervoustissue associated with a dermatome.

Spinal tissue can include the ascending and descending tracts of thespinal cord, more specifically, the ascending tracts of that compriseintralaminar neurons or the dorsal column. For example, the spinaltissue can include neuronal tissue associated with any of the cervicalvertebral segments (C1, C2, C3, C4, C5, C6, C7 and C8) and/or any tissueassociated with any of the thoracic vertebral segments (T1, T2, T3, T4,T5, T6, T7, T8, T9, T10, T11, T12) and/or any tissue associated with anyof the lumbar vertebral segments (L1, L2, L3, L4. L5, L6) and/or anytissue associated with the sacral vertebral segments (S1, S2, S3, S4,S5). More specifically, the spinal tissue is the dorsal column of thespinal cord. The brainstem tissue can include the medulla oblongata,pons or mesencephalon, more particular the posterior pons or posteriormesencephalon, Lushka's foramen, and ventrolateral part of the medullaoblongata.

In other embodiments, the stimulation leads are positioned incommunication with the neuronal tissue of the spinal cord, morespecifically, the dorsal column of the spinal cord. For example,stimulation electrodes are commonly positioned external to the duralayer surrounding the spinal cord. Stimulation on the surface of thecord is also contemplated, for example, stimulation may be applied tothe spinal cord tissue as well as to the nerve root entry zone.Stimulation electrodes may be positioned in various body tissues and incontact with various tissue layers; for example, subdural, subarachnoid,epidural, and cutaneous, and/or subcutaneous implantation is employed insome embodiments.

Spinal cord stimulation can be accomplished utilizing eitherpercutaneous leads and/or laminotomy type leads that comprise a paddle.Percutaneous leads commonly have two or more equally-spaced electrodeswhich are placed above the dura layer through the use of a Touhy-likeneedle. For insertion, the Touhy-like needle is passed through the skinbetween desired vertebrae to open above the dura layer.

In contrast to the percutaneous leads, laminotomy leads have a paddleconfiguration and typically possess a plurality of electrodes (forexample, two, four, eight, sixteen or twenty) arranged in one or morecolumns. Implanted laminotomy leads are commonly transversely centeredover the physiological midline of a patient. In such position, multiplecolumns of electrodes are well suited to address both unilateral andbilateral pain, where electrical energy may be administered using eithercolumn independently (on either side of the midline) or administeredusing both columns to create an electric field which traverses themidline. A multi-column laminotomy lead enables reliable positioning ofa plurality of electrodes, and in particular, a plurality of electrodecolumns that do not readily deviate from an initial implantationposition.

Laminotomy leads require a surgical procedure for implantation. Thesurgical procedure, or partial laminectomy, requires the resection andremoval of certain vertebral tissue to allow both access to the dura andproper positioning of a laminotomy lead. The laminotomy lead offers amore stable platform, which is further capable of being sutured in placethat tends to migrate less in the operating environment of the humanbody. Depending on the position of insertion, however, access to thedura may only require a partial removal of the ligamentum flavum at theinsertion site. In some embodiments, two or more laminotomy leads may bepositioned within the epidural space, and the leads may assume anyrelative position to one another.

In certain embodiments, the stimulation leads may be placedsubcutaneously on the patient's head. For example, one or morestimulation leads can be implanted subcutaneously such that one or morestimulation electrodes are positioned in communication with a dermatomearea, for example (C1, C2, C3, C4, C5, C6, C7, and C8), cervical nerveroots (e.g., C1, C2, C3, C4, C5, C6, C7 and C8) cranial nerves (e.g.,olfactory nerve, optic, nerve, oculomotor nerve, trochlear nerve,trigeminal nerve, abducent nerve, facial nerve, vestibulocochlear nerve,glossopharyngeal nerve, vagal nerve, accessory nerve, and hypoglossalnerve) and/or occipital area For example, one or more stimulationelectrodes are positioned in the C2 dermatome area/C3 dermatome area,subcutaneously, but superior to the galea. Within certain areas of theC2 dermatome area or occipital or occiput area, there is little or nomuscle, this area primarily consists of fat, fascia, perostium, andneurovascular structures (e.g., galea). More specifically, the electrodecan be implanted in a subcutaneous fashion such that the electrode ispositioned below the skin, above the bone on the back of the head orsuperior to the periosteum. On the back of the head, the probe ispositioned in the C2 dermatome area or positioned at the back of thepatient's head at about the level of the ear.

C. Brainstem Stimulation

Implantation of a stimulation lead in communication with thepredetermined brainstem area can be accomplished via a variety ofsurgical techniques that are well known to those of skill in the art.For example, an electrical stimulation lead can be implanted on, in, ornear the brainstem by accessing the brain tissue through a percutaneousroute, an open craniotomy, or a burr hole. Where a burr hole is themeans of accessing the brainstem, for example, stereotactic equipmentsuitable to aid in placement of an electrical stimulation lead on, in,or near the brainstem may be positioned around the head. Anotheralternative technique can include, a modified midline or retrosigmoidposterior fossa technique.

In certain embodiments, electrical stimulation lead is located at leastpartially within or below the dura mater adjacent the brainstem.Alternatively, a stimulation lead can be placed in communication withthe predetermined brainstem area by threading the stimulation lead upthe spinal cord column, as described above, which is incorporatedherein.

Still further, a predetermined brainstem area can be indirectlystimulated by implanting a stimulation lead in communication with acranial nerve (e.g., olfactory nerve, optic, nerve, oculomotor nerve,trochlear nerve, trigeminal nerve, abducent nerve, facial nerve,vestibulocochlear nerve, glossopharyngeal nerve, vagal nerve, accessorynerve, and the hypoglossal nerve) as well as high cervical nerves(cervical nerves have anastomoses with lower cranial nerves) such thatstimulation of a cranial nerve indirectly stimulates the predeterminedbrainstem tissue. Such techniques are further described in U.S. Pat.Nos. 6,721,603; 6,622,047; and 5,335,657 each of which are incorporatedherein by reference.

IV. Generation of Stimulation Parameters and Modifications Thereof

Conventional neuromodulation devices can be modified to apply a 1/f^(β)noise stimulation, or 1/f^(β) noise stimulation in combination withindividual peak frequencies (e.g., alpha, beta, theta and delta) orcombination of 1/f^(β) noise stimulation combined with burst or tonicstimulation to nerve tissue of a patient by modifying the softwareinstructions and/or stimulation parameters stored in the devices.Specifically, conventional neuromodulation devices typically include amicroprocessor and a pulse generation module. The pulse generationmodule generates the electrical pulses according to a defined pulsewidth and pulse amplitude and applies the electrical pulses to definedelectrodes through switching circuitry and the wires of a stimulationlead. The microprocessor controls the operations of the pulse generationmodule according to software instructions stored in the device andaccompanying stimulation parameters. Examples of commercially availableneuromodulation devices that can be modified according to someembodiments include the EON® or EON Mini®, manufactured by St. JudeMedical. Other neuromodulation devices that may be modified can include,LIBRA® or BRIO® manufactured by St. Jude Medical.

These neuromodulation devices can be adapted by modifying the softwareinstructions provided within the neuromodulation devices used to controlthe operations of the devices. In some embodiments, software is providedwithin the neuromodulation device to retrieve or generate a stream ofdigital values that define a waveform according to the desired powerspectral density. This stream of values is then employed to control theamplitude of successive stimulation pulses generated by theneurostimulation device. The software may include a pseudo-random numbergenerator according to known algorithms to generate the stream ofdigital values. Alternatively, one or more streams of digital valueshaving the desired power spectral density may be generated offline andstored in memory of the neuromodulation device (in a compressed or othersuitable format). The software of the neuromodulation device mayretrieve the values from memory for control of the amplitude of theoutput pulses of the neuromodulation device. Alternatively, an externalconventional neuromodulation devices can be used (for example, theDS8000™ digital stimulator available from World Precision Instruments)to generate the desired electrical stimulation. For example, a customwaveform may be generated offline on a personal computer and importedinto the digital stimulator for pulse generation. Signal parameters maybe inputted, such as 1/f^(β) noise spectrum, for example FIG. 3A or FIG.4A, into suitable waveform generating software to generate the stream ofdigital values. Alternatively, depending upon the capabilities of theexternal digital stimulator, the stream of digital values may becalculated on board the processor of the external digital stimulator.

FIG. 2 depicts an exemplary neuromodulation device that can be used toprovide the desired stimulation. Signal parameters are inputted, such as1/f^(β) noise spectrum, for example FIG. 3A or FIG. 4A, into thesoftware or memory 210 and the desired wave pattern or signals aregenerated using microprocessor 220. A standard digital-to-analogconverter 230 receives the calculated digital signals and generatesanalog output pulses corresponding to the values of the digital signals.The generated output pulses may be outputted from the neuromodulationdevice through an output capacitor. Optionally, any suitable filter 240can be used to smooth or shape the signals; however, unsmoothed orunfiltered signals can be transmitted to the switching circuitry 250which provides the signals to the electrodes 100 thereby stimulating theneuronal tissue using the desired 1/f^(β) noise stimulation pattern. Asan example, the stimulator design disclosed in U.S. Pat. No. 7,715,912may be employed to generate stimulation pulses according to the desiredstimulation pattern. FIGS. 3B and 4B illustrate exemplary waveformsgenerated by external generators and provided to the electrodes tostimulate neuronal tissue with the 1/f^(β) noise stimulation pattern.

In addition to providing a stimulation waveform similar to that of1/f^(β) noise spectrum; it may be desirable to modify the 1/f^(β) noisewaveform stimulation pattern. Such modifications can utilize theaddition of peak frequencies, such as the addition of an alpha, beta,theta, and/or delta peaks to the 1/f^(β) noise spectrum waveform, seefor example, FIGS. 5A and 5B. Such frequency peaks can be obtained byusing standard peaks or individualizing the frequency peaks. Suchinformation can be communicated to the microprocessor 220 via thesoftware component 210. Thus, the data communicated can comprisestandard frequency peaks or comprise individualized frequency peaks orpatient specific. The patient specific frequency peaks can be obtainedoff-line or in real time or on-line, for example prior to implantationor at any time point after implantation, for example, during the initialprogramming of the IPG. Any suitable signal processing technique may beemployed to add the appropriate spectral peaks. For example, a suitablefilter may be applied to the noise signal. Alternatively, a separatesignal may be generated with a spectral peak about the desired frequencyand the separate signal may be added to or superimposed on the noisesignal.

With reference to FIG. 6, with electrodes disposed near, adjacent to,directly next to or within the target neuronal tissue, for example,brain tissue, some representative embodiments utilize the detection andanalysis of neuronal activity, such as EEG measurements. Specifically,terminals of the lead, such as an EEG lead, may be coupled usingrespective conductors 601 to external controller that contains suitablecircuitry to analyze neuronal activity, for example, an EEG analyzer canbe included in the external controller in which the analyzer functionsare adapted to receive EEG signals from the electrodes and process theEEG signals to identify frequency peaks, such as LORETA software can beused. Further signal processing may occur on a suitable computerplatform within the external controller using available signalprocessing. The computer platform may include suitable signal processingalgorithms (e.g., time domain segmentation, FFT processing, windowing,logarithmic transforms, etc.). Further platforms or algorithms to modifythe signals are included in the modification algorithms (e.g., envelopemodification, etc). User interface software may be used to present theprocessed neuronal activity (i.e., specific peak frequency) and combinea specific peak frequency with the 1/f^(β) noise stimulation waveformpatterns to the transmitter 603 which then transmits, for example, viaradio frequency to the IPG 604 which is adapted to provide the 1/f^(β)noise stimulation waveform patterns with the peak frequency to achievestimulation of the target neuronal tissue via electrode 100. Thisprocedure can be performed on-line or off-line. Additionally, IPG 604preferably comprises circuitry such as an analog-to-digital (AD)converter, switching circuitry, amplification circuitry, transmitters,and/or filtering circuitry.

Still further, it may be desirable to utilize another implantable devicethat is capable of performing the functions of the external controller.Thus, those of skill in the art can modify an implantable device suchthat it is capable of detecting/sampling and processing of the signalsrepresentative of the neuronal activity/EEG activity. Such a device mayinclude a microprocessor that is capable of performing these activitiesas well as a transmitter such that the signals can be transmitted viaradiofrequency to another implantable device, such as described above inFIG. 6 that is capable of generating the desired signal to the targettissue. Thus, an EEG lead is placed or positioned near the target braintissue via methods known to those of skill in the art. The EEG leaddetects neuronal activity which is relayed to the processor thatpossesses sufficient computational capacity to collect the informationobtained from the EEG electrode, process it to obtain the respectivefrequency peak desired and/or modulate the frequency peaks and transmitthe frequency to an RF transmitter that transmits the respectiveinformation to microprocessor located in the stimulation IPG.

Another means to modify the 1/f^(β) waveform stimulation pattern is tocombine it with tonic stimulation or burst stimulation as described inU.S. Pat. No. 7,734,340, issued Jun. 8, 2010 and U.S. patent applicationSer. No. 12/109,098, filed Apr. 24, 2008, both of which are incorporatedby reference in their entirety. Thus, a neuromodulation device can beimplemented to apply either burst or tonic stimulation using a digitalsignal processor and one or several digital-to-analog converters. Theburst stimulus and/or tonic stimulus waveform could be defined in memoryand applied to the digital-to-analog converter(s) for applicationthrough electrodes of the medical lead. The digital signal processorcould scale the various portions of the waveform in amplitude and withinthe time domain (e.g., for the various intervals) according to thevarious burst and/or tonic parameters. A doctor, the patient, or anotheruser of stimulation source may directly or indirectly input stimulationparameters to specify or modify the nature of the stimulation provided.

Thus, a microprocessor and suitable software instructions to implementthe appropriate system control can be used to control the burst and/ortonic stimulation in combination with the 1/f^(β) stimulation. Theprocessor can be programmed to use “multi-stim set programs” which areknown in the art. A “stim set” refers to a set of parameters whichdefine a pulse to be generated. For example, a stim set defines pulseamplitude, a pulse width, a pulse delay, and an electrode combination.The pulse amplitude refers to the amplitude for a given pulse and thepulse width refers to the duration of the pulse. The pulse delayrepresents an amount of delay to occur after the generation of the pulse(equivalently, an amount of delay could be defined to occur before thegeneration of a pulse). The amount of delay represents an amount of timewhen no pulse generation occurs. The electrode combination defines thepolarities for each output which, thereby, controls how a pulse isapplied via electrodes of a stimulation lead. Other pulse parameterscould be defined for each stim set such as pulse type, repetitionparameters, etc. Still further, the 1/f^(β) waveform stimulation patternalone or in combination with either burst and/or tonic may beimplemented such that the stimulation occurs either sequentially,randomly or pseudo-sequentially over multiple poles or electrodes on thestimulation lead.

In certain embodiments, the stimulation parameters may comprise a burststimulation having a frequency in the range of about 1 Hz to about 300Hz in combination with a tonic stimulation having a frequency in therange of about 1 Hz to about 300 Hz. Those of skill in the art realizethat the frequencies can be altered depending upon the capabilities ofthe IPGs that are utilized. More particularly, the burst stimulation maybe at about 6, 18, 40, 60, 80, 100, 150, 200, 250 or 300 Hz consistingof 5 spikes with 1 ms pulse width, 1 ms interspike interval incombination with 1/f^(β) signals interspersed between or around theburst or prior to or after the burst or in any variation thereofdepending upon the efficacy of treatment. Still further, 1/f^(β) signalsor stimulation paradigm as described herein may be used in combinationwith about 6, 18, 40, 60, 80, 100, 150, 200, 250, 300 Hz tonicstimulation interspersed between or around the 1/f^(β) signals orstimulation paradigm, or any variation thereof depending upon theefficacy of treatment and the capabilities of the IPG.

Still further, those of skill in the art recognize that burst firingrefers to an action potential that is a burst of high frequency spikes(300-1000 Hz) (Beurrier et al., 1999). Burst firing acts in a non-linearfashion with a summation effect of each spike and tonic firing refers toan action potential that occurs in a linear fashion.

Yet further, burst can refer to a period in a spike train that has amuch higher discharge rate than surrounding periods in the spike train(N. Urbain et al., 2002). Thus, burst can refer to a plurality of groupsof spike pulses. A burst is a train of action potentials that, possibly,occurs during a ‘plateau’ or ‘active phase’, followed by a period ofrelative quiescence called the ‘silent phase’ (Nunemaker, CellscienceReviews Vol 2 No. 1, 2005.) Thus, a burst comprises spikes having aninter-spike interval in which the spikes are separated by 0.5milliseconds to about 100 milliseconds. Those of skill in the artrealize that the inter-spike interval can be longer or shorter. Yetfurther, those of skill in the art also realize that the spike ratewithin the burst does not necessarily occur at a fixed rate; this ratecan be variable. A spike refers to an action potential. Yet further, a“burst spike” refers to a spike that is preceded or followed by anotherspike within a short time interval (Matveev, 2000), in other words,there is an inter-spike interval, in which this interval is generallyabout 100 ms but can be shorter or longer, for example 0.5 milliseconds.

Still further, it may be of interest to use a system that includes aprocessor that determines whether the patient is in a sleep state, andcontrols therapy based upon the sleep state. The sleep state may berelevant for 1/f^(β) noise stimulation therapy if during a given sleepstage the patient's frequency spectrum changes, for example, the highfrequency is adjusted such that the spectrum moves from pink or brownnoise to black noise. For example, FIG. 7 shows 1/f² (brown noise)activity at rest in a human tinnitus patient and in normal patients. Atrest, the brain has an activity at 1/f² (brown noise) for the normalpatients and the tinnitus patients tend to have an activity at 1/f¹⁻²(between pink and brown noise)

As referred to herein, the sleep state may refer to a state in whichpatient is intending on sleeping (e.g., initiating thoughts of sleep),is at rest, is attempting to sleep or has initiated sleep and iscurrently sleeping. In addition, the processor may determine a sleepstage of the sleep state based on a biosignal detected within brain thepatient and control therapy delivery to patient based on a determinedsleep stage. Examples of biosignals include, but are not limited to,electrical signals generated from local field potentials within one ormore regions of brain, such as, but not limited to, anelectroencephalogram (EEG) signal or an electrocorticogram (ECOG)signal. The biosignals that are detected may be detected within the sametissue site of brain as the target tissue site for delivery ofelectrical stimulation. In other examples, the biosignals may bedetected within another tissue site.

Within a sleep state, the patient may be within one of a plurality ofsleep stages. Example sleep stages include, for example, Stage 1 (alsoreferred to as Stage N1 or S1), Stage 2 (also referred to as Stage N2 orS2), Deep Sleep (also referred to as slow wave sleep), and rapid eyemovement (REM). The Deep Sleep stage may include multiple sleep stages,such as Stage N3 (also referred to as Stage S3) and Stage N4 (alsoreferred to as Stage S4). In some cases, the patient may cycle throughthe Stage 1, Stage 2, Deep Sleep, REM sleep stages more than once duringa sleep state. The Stage 1, Stage 2, and Deep Sleep stages may beconsidered non-REM (NREM) sleep stages.

FIG. 8 shows an exemplary implantable neuromodulation device 800 thatcan be used to determine a stage of sleep and adjust therapy. Forexample, the device may include, processor 802, memory 801, stimulationgenerator 804, sensing module 805, telemetry module 806, and sleep stagedetection module 803. Although sleep stage detection module 803 is shownto be a part of processor 802 in FIG. 7, in other examples, sleep stagedetection module 803 and processor 802 may be separate components andmay be electrically coupled, e.g., via a wired or wireless connection.

Memory 801, as shown in FIG. 9, may include any volatile or non-volatilemedia, such as a random access memory (RAM), read only memory (ROM),non-volatile RAM (NVRAM), electrically erasable programmable ROM(EEPROM), flash memory, and the like. Memory 801 may store instructionsfor execution by processor 802 and information defining therapy deliveryfor the patient, such as, but not limited to, therapy programs ortherapy program groups, information associating therapy programs withone or more sleep stages, thresholds or other information used to detectsleep stages based on biosignals, and any other information regardingtherapy of the patient. Therapy information may be recorded in memory801 for long-term storage and retrieval by a user. As described infurther detail with reference to FIG. 9, memory 801 may include separatememories for storing information, such as separate memories for therapyprograms 900, and sleep stage information 901. Yet further, othermemories that may be stored may include patient information, such asinformation relating to specific peak frequencies, or informationrelating to 1/f^(β) stimulation.

It is also envisaged that the recording electrode can be used to recordor detect sleep stage or when a subject is not in a sleep stage, therecording electrode can be used to detect a change in the normalspectral composition of the noise and adjust the parameters of thestimulation therapy, for example, adjust the stimulation factors such asdrowsiness, stress, depression, excitement, arousal, alcohol or otherdrug intake etc.

V. Treating Neurological Conditions

The present stimulation method acts to stimulate neuronal tissue whichin turn stimulate the neuronal tissue to cause/allow the tissue to actin the best interest of the host through use of the its naturalmechanisms.

Accordingly, the present methods and/or devices relate to modulation ofneuronal activity to affect neurological, neuropsychological orneuropsychiatric activity. The present method finds particularapplication in the modulation of neuronal function or processing toaffect a functional outcome. The modulation of neuronal function isparticularly useful with regard to the prevention, treatment, oramelioration of neurological, psychiatric, psychological, consciousstate, behavioral, mood, and thought activity (unless otherwiseindicated these will be collectively referred to herein as “neurologicalactivity” which includes “psychological activity” or “psychiatricactivity”). When referring to a pathological or undesirable conditionassociated with the activity, reference may be made to a neurologicaldisorder which includes “psychiatric disorder” or “psychologicaldisorder” instead of neurological activity or psychiatric orpsychological activity. Although the activity to be modulated usuallymanifests itself in the form of a disorder such as a attention orcognitive disorders (e.g., Autistic Spectrum Disorders); mood disorder(e.g., major depressive disorder, bipolar disorder, and dysthymicdisorder) or an anxiety disorder (e.g., panic disorder, posttraumaticstress disorder, obsessive-compulsive disorder and phobic disorder);neurodegenerative diseases (e.g., multiple sclerosis, Alzheimer'sdisease, amyotrophic lateral sclerosis (ALS), Parkinson's disease,Huntington's Disease, Guillain-Barre syndrome, myasthenia gravis, andchronic idiopathic demyelinating disease (CID)), movement disorders(e.g., dyskinesia, tremor, dystonia, chorea and ballism, tic syndromes,Tourette's Syndrome, myoclonus, drug-induced movement disorders,Wilson's Disease, Paroxysmal Dyskinesias, Stiff Man Syndrome andAkinetic-Ridgid Syndromes and Parkinsonism), epilepsy, tinnitus, pain,phantom pain, diabetes neuropathy, one skilled in the art appreciatesthat the invention may also find application in conjunction withenhancing or diminishing any neurological or psychiatric function, notjust an abnormality or disorder. Neurological activity that may bemodulated can include, but not be limited to, normal functions such asalertness, conscious state, drive, fear, anger, anxiety, repetitivebehavior, impulses, urges, obsessions, euphoria, sadness, and the fightor flight response, as well as instability, vertigo, dizziness, fatigue,photophobia, concentration dysfunction, memory disorders, headache,dizziness, irritability, fatigue, visual disturbances, sensitivity tonoise (misophonia, hyperacusis, photophobia), judgment problems,depression, symptoms of traumatic brain injury (whether physical,emotional, social or chemical), autonomic functions, which includessympathetic and/or parasympathetic functions (e.g., control of heartrate), somatic functions, and/or enteric functions. Thus, the presentmethods and/or devices encompass modulation of central and/or peripheralnervous systems.

Other neurological disorders can include, but are not limited toheadaches, for example, migraine, trigeminal autonomic cephalgia(cluster headache (episodic and chronic)), paroxysmal hemicrania(episodic and chronic), hemicrania continua, SUNCT (shortlastingunilateral neuralgiform headache with conjunctival injection andtearing), cluster tic syndrome, trigeminal neuralgia, tension typeheadache, idiopathic stabbing headache, etc. The neurostimulation devicecan be implanted intracranially or peripherally, for example, but notlimited to implanting a neurostimulation device occipitally for thetreatment of headaches.

Autonomic and/or enteric nervous system disorders that can be treatedusing the stimulation system and/or method of the present inventioninclude, but are not limited to hypertension, neurosis cordis or heartrhythm disorders, obesity, gastrointestinal motion disorders,respiratory disorders, diabetes, sleep disorders, snoring, incontinenceboth urologic and gastrointestinal, sexual dysfunction, chronic fatiguesyndrome, fibromyalgia, whiplash associated symptoms, post-concussionsyndrome, posttraumatic stress disorder etc.

Yet further immunological disorders may also be treated using thestimulation system and/or method of the present invention. This is basedon the fact that the immune system senses antigens coordinates'metabolic, endocrine and behavioral changes that support the immunesystem and modulates the immune system via neuroendocrine regulation anddirect immune cell regulation. Such immunological disorders include,such as allergy, rhinitis, asthma, rheumatoid arthritis, psoriasisarthritis, lupus erythematosus disseminatus, multiple sclerosis andother demyelinating disorders, autoimmune thyroiditis, Crohn's disease,diabetes mellitus etc.

Still further tumoral disorders, both malignant and benign may also betreated using the stimulation system and/or method of the presentinvention. This is based on the fact that tumoral behavior is linked toimmunological function. This is seen in immunodeficiency syndromes suchas AIDS and hematological disorders, where multiple and different tumorsdevelop. In this setting neuromodulation could indirectly influencetumoral behavior.

Yet further neuroendocrine disorders may also be treated using thestimulation system and/or method of the present invention. Suchdisorders are stress reactions, hypothalamic-pituitary axis dysfunction,etc.

Yet further functional disorders may also be treated using thestimulation system and/or method of the present invention. Suchdisorders can be anorexia, bulimia, phobias, addictions, paraphilia,psychosis, depression, bipolar disorder, kleptomania, aggression, orantisocial sexual behavior. One skilled in the art appreciates that theinvention may also find application in conjunction with enhancing ordiminishing any neurological or psychiatric function, not just anabnormality or disorder.

Using the above described stimulation system, the predetermined site ortarget area is stimulated in an effective amount or effective treatmentregimen to decrease, reduce, modulate or abrogate the neurologicaldisorder or condition. Thus, a subject or patient is administered atherapeutically effective stimulation so that the subject has animprovement in the parameters relating to the neurological disorder orcondition including subjective measures such as, for example,neurological examinations and neuropsychological tests (e.g., MinnesotaMultiphasic Personality Inventory, Beck Depression Inventory,Mini-Mental Status Examination (MMSE), Hamilton Rating Scale forDepression, Wisconsin Card Sorting Test (WCST), Tower of London, Strooptask, MADRAS, CGI, N-BAC, or Yale-Brown Obsessive Compulsive score(Y-BOCS)), motor examination, visual analog scale (VAS) and cranialnerve examination, and objective measures including use of additionalpsychiatric medications, such as anti-depressants, or other alterationsin cerebral blood flow or metabolism and/or neurochemistry.

Patient outcomes may also be tested by health-related quality of life(HRQL) measures: Patient outcome measures that extend beyond traditionalmeasures of mortality and morbidity, to include such dimensions asphysiology, function, social activity, cognition, emotion, sleep andrest, energy and vitality, health perception, normal eating habits orbehaviors (i.e., regained appetite or reduced appetite) and general lifesatisfaction. (Some of these are also known as health status, functionalstatus, or quality of life measures.)

Treatment regimens may vary as well, and often depend on the health andage of the patient. Obviously, certain types of disease will requiremore aggressive treatment, while at the same time; certain patientscannot tolerate more taxing regimens. The clinician will be best suitedto make such decisions based on the known subject's history.

For purposes of this invention, beneficial or desired clinical resultsinclude, but are not limited to, alleviation of symptoms, improvement ofsymptoms, diminishment of extent of disease, stabilized (i.e., notworsening) state of disease, delay or slowing of disease progression,amelioration or palliation of the disease state, and remission (whetherpartial or total), whether objective or subjective. The improvement isany observable or measurable improvement. Thus, one of skill in the artrealizes that a treatment may improve the patient condition, but may notbe a complete cure of the disease.

In certain embodiments, in connection with improvement in one or more ofthe above or other neurological disorders, the electrical stimulationmay have a “brightening” effect on the person such that the person looksbetter, feels better, moves better, thinks better, and otherwiseexperiences an overall improvement in quality of life, (e.g., selfconfidence, alleviating shyness, distrust etc).

In certain embodiments, the neuromodulation method described herein isutilized to treat a subject suffering from or suspected of sufferingfrom tinnitus. Thus, a subject is administered a therapeuticallyeffective stimulation so that the subject has an improvement in theparameters relating to tinnitus including informal questioning of thesubject, formal subjective testing and analysis according to one or moreaudiology test, for example the Goebel tinnitus questionnaire or othervalidated tinnitus questionnaires, audiometry, tinnitus matching,impedance, BAEP, and OAE. The improvement is any observable ormeasurable improvement. Thus, one of skill in the art realizes that atreatment may improve the patient condition, but may not be a completecure of the disease.

In other embodiments, the neuromodulation method described herein isutilized to treat a subject suffering from or suspected of sufferingfrom pain. One example of a method for pain measurement is the use ofthe Visual Analog Scale (VAS). In the VAS patients are asked to ranktheir pain by making a mark on a bar that is labeled “no pain” on oneend, and “pain as bad as possible” on the other end. Patients may markthe bar anywhere between the two opposite poles of perceived painsensation. This mark can then be given any quantitative value such asfractional, decimal or integer values by the clinician and used as asemi-quantitative pain measurement. In various tests for pain severity,patients may rank their pain on a scale between zero and ten, by a scaleof faces depicting various emotions from happy to very sad and upset,and by answering a variety of questions describing the pain. Inpreferred embodiments, the patient's pain is assessed prior to andduring a trial implantation procedure. In other embodiments, informalsubjective questioning of the person, and/or formal subjective testingand analysis may be performed to determine whether the subject's painhas sufficiently improved throughout trial stimulation.

In addition to utilizing pain scores and grading and objective measuresincluding use of additional pain medications (e.g., reduction in theamount of medication consume or elimination of the consumption of painmedications), other methods to determine improvement of a patient's painmay comprise administering various standardized questionnaires or teststo determine the patient's neuropsychological state as described above.

If the subject's neurological disorder/disease has not sufficientlyimproved, or if the reduction of the neurological disorder/disease isdetermined to be incomplete or inadequate during an intra-implantationtrial stimulation procedure, stimulation lead may be moved incrementallyor even re-implanted, one or more stimulation parameters may beadjusted, or both of these modifications may be made and repeated untilat least one symptom associated with the neurological disorder/diseasehas improved.

Where appropriate, post-implantation trial stimulation may be conductedto determine the efficacy of various types of burst and tonicstimulation. Examples of efficacy metrics may include the minimumrequired voltage for a given protocol to achieve maximum and/ortherapeutic benefits to the neurological disease and/or disorder.Efficacy metrics may also include a measurement of the presence and/ordegree of habituation to a given protocol over one or more weeks ormonths, and any necessary modifications made accordingly. Suchassessments can be conducted by suitable programming, such as thatdescribed in U.S. Pat. No. 5,938,690, which is incorporated by referencehere in full. Utilizing such a program allows an optimal stimulationtherapy to be obtained at minimal power. This ensures a longer batterylife for the implanted systems.

In certain embodiments, it may be desirable for the patient to controlthe therapy to optimize the operating parameters to achieve increased oroptimized the treatment. For example, the patient can alter the pulsefrequency, pulse amplitude and pulse width using a hand held radiofrequency device that communicates with the IPG. Once the operatingparameters have been altered by the patient, the parameters can bestored in a memory device to be retrieved by either the patient or theclinician. Yet further, particular parameter settings and changestherein may be correlated with particular times and days to form apatient therapy profile that can be stored in a memory device.

VI. Example

The following are examples provided herein. It should be appreciated bythose of skill in the art that the techniques disclosed in the exampleswhich follow represent techniques discovered by the inventors tofunction well in the practice of the invention, and thus can beconsidered to constitute preferred modes for its practice. However,those of skill in the art should, in light of the present disclosure,appreciate that many changes can be made in the specific embodimentswhich are disclosed and still obtain a like or similar result withoutdeparting from the spirit and scope of the invention.

In the clinical setting, patients were implanted to treat pain ortinnitus.

Materials and Methods

Patients having spasticity, phantom pain, facial pain or tinnitus wereimplanted with electrodes for stimulation therapy using 1/f^(B) noisestimulation patterns. The patients were implanted with the electrodes(Lamitrode 44 stimulation lead available from ANS Medical, Plano, Tex.,USA). In most patients, the electrodes (Lamitrode 44 stimulation leadavailable from ANS Medical, Plano, Tex., USA) were implanted in theauditory cortex, and one patient was implanted with a cervical dorsalcolumn stimulation electrode (Lamitrode 44 stimulation lead). Prior tothe use of 1/f^(B) noise stimulation patterns, all patients underwentburst stimulation at 6, 18, or 40 Hz consisting of 5 spikes with 1 mspulse width, 1 ms interspike interval in a charged balanced manner and6, 18, or 40 Hz tonic mode interspersed between or around the bursts.The stimuli were delivered by an 8 channel digital neurostimulator(DS8000, World Precision Instruments, Hertfordshire, England/Sarasota,Fla., USA), capable of delivering tonic and burst mode stimulation.Next, 1/f^(B) noise stimulation patterns was used to determine if1/f^(B) noise stimulation patterns resulted in more improvement of thesymptoms or reduces the risk of epileptic events. Three patientsreceived constant 1/f^(B) noise stimulation for >1.5 hrs without anepileptic event. The stimuli were delivered by an 8 channel digitalneurostimulator (DS8000, World Precision Instruments, Hertfordshire,England/Sarasota, Fla., USA), capable of delivering 1/f^(B) noisestimulation, see for example FIGS. 3A and 3B.

In another patient, the stimulation was altered by adding a beta peakfrequency; see for example, FIGS. 5A and 5B.

Results

The below Table 1 shows VAS scores for patients that had burst, tonicand then had noise stimulation or 1/f^(β) stimulation. The table showsthat by 1/f^(β) stimulation parameters patients suffering tinnitus,spasticity, phantom pain and facial can be treated with improvedbenefits of no epileptic events measured during constant stimulationfor >1.5 hrs. Yet further, the below table also shows that if thepatient responds to burst or tonic stimulation, then the patient willrespond to 1/f^(β) stimulation parameters, and if the patient does notrespond to burst or tonic stimulation, then they will probably notrespond to 1/f^(β) stimulation parameters. This lack of response may bean indication that the stimulation site is not optimal and a differentsite should be examined or investigated.

NOISE STIMULATION Post 1/f^(β) noise pulse alpha peak modulatedPre-operative prestimulation stimulation spasticity 7 6 4 phantom pain 95.5 3.5 dorsal column 8 6 4 stimulation tinnitus 8 7 6.5 tinnitus 10 9.58 tinnitus 10 7 7 Facial pain 7 6.5 5.5 tinnitus 9 7 6 Tinnitus 9 8 7Tinnitus 8 8 8 Tinnitus 10 10 10 Tinnitus 8 8 8 Facial pain 8 8 8 * =after tonic or burst stimulation

CONCLUSIONS

At least three patients were stimulated constantly for more than onehour without inducing an epileptic event. Thus, this type of stimulationparadigm is anti-epileptic and will prevent habituation because itmimics natural oscillations and has a longer lasting residual inhibitionwhich will limit battery utilization and limit the amount of currentthat is used to stimulate the brain.

As will be recognized by those skilled in the art, the innovativeconcepts described in the present application can be modified and variedover a wide range of applications. Accordingly, the scope of patentedsubject matter should not be limited to any of the specific exemplaryteachings discussed above, but is instead defined by the followingclaims.

What is claimed:
 1. A method of stimulating nerve tissue of a patientusing a pulse generator, the method comprising: generating, by a pulsegenerator, a stimulus that comprises a signal that is produced from afrequency spectrum having a power spectral density per unit of bandwidthproportional to 1/f^(β), wherein β is excludes 0; providing the stimulusfrom the pulse generator to at least one stimulation lead; and applyingthe stimulus to nerve tissue of the patient via one or severalelectrodes of the at least one stimulation lead.
 2. The method of claim1, wherein β=1.
 3. The method of claim 1, wherein β=2.
 4. The method ofclaim 1, wherein the stimulus is combined with at least one pulsestimulus to be repeated in a tonic manner.
 5. The method of claim 1,wherein the stimulus is combined with a burst stimulus that comprises aplurality of groups of spike pulses.
 6. The method of claim 1, whereinthe stimulus is combined with at least one pulse stimulus to be repeatedin a tonic manner and with a burst stimulation that comprises aplurality of groups of spike pulses.
 7. The method of claim 1, whereinthe stimulus is modulated at any a specific frequency, either byselective power increase, envelope modulation or adding more tonic orburst stimuli of this frequency.
 8. A method of stimulating nerve tissueof a patient using a pulse generator, the method comprising: storing, inthe pulse generator, one first stimulation parameter that defines afrequency to be used as the lower bound of a frequency spectrum;storing, in the pulse generator, one second stimulation parameter thatdefines a frequency to be used as the upper bound of a frequencyspectrum; generating, by pulse generator, a stimulus that comprises afrequency spectrum between the first stimulation parameter and secondstimulation parameter, wherein the frequency and power of the frequencyspectrum are inversely proportional; providing the stimulus from theimplantable pulse generator to at least one stimulation lead; andapplying the stimulus to nerve tissue of the patient via at least oneelectrodes of the at least one stimulation lead.
 9. The method of claim8 wherein the stimulus is further defined as having a frequency spectrumof 1/f^(β), wherein β excludes
 0. 10. The method of claim 8, whereinβ=1.
 11. The method of claim 8, wherein β=2.
 12. The method of claim 8,wherein the stimulus is combined with at least one stimulation pulse tobe repeated in a tonic manner.
 13. The method of claim 8, wherein thepink noise stimulus is combined with a burst stimulus that comprises aplurality of groups of spike pulses.
 14. A method of stimulating nervetissue of a patient using a pulse generator, the method comprising:storing, in the pulse generator, one first stimulation parameter thatdefines a frequency to be used as the lower bound of a frequencyspectrum; storing, in the pulse generator, one second stimulationparameter that defines a frequency to be used as the upper bound of afrequency spectrum; storing, in pulse generator, one third stimulationparameter that defines a frequency at which a peak of a pre-determinedamplitude is to occur; generating, by pulse generator, a stimulus thatcomprises a frequency spectrum between the first stimulation parameterand second stimulation parameter, wherein the power spectral density isinversely proportional to the frequency, wherein a peak of apredetermined amplitude occurs at the frequency defined by the thirdstimulation parameter; providing the stimulus from the pulse generatorto at least one stimulation lead; and applying the stimulus to nervetissue of the patient via one or several electrodes of the at least onestimulation lead.
 15. The method of claim 14, wherein the noise stimulusis combined with at least one stimulation pulse to be repeated in atonic manner and with a burst stimulation that comprises a plurality ofgroups of spike pulses.
 16. The method of claim 14, wherein the peakoccurs at a frequency between 0 and 4 Hertz.
 17. The method of claim 14,wherein the peak occurs at a frequency between 4 and 7 Hertz.
 18. Themethod of claim 14, wherein the peak occurs at a frequency between 8 and12 Hertz.
 19. The method of claim 14, wherein the peak occurs at afrequency between 12 and 30 Hertz.